The prostate is a gland about the size and shape of a walnut. The prostate is located between the pubic bone and rectum. It surrounds the upper part of the urethra, the tube that carries urine from the bladder. As a man ages, his prostate may change. Non-cancerous (benign) growths may form. Or some cells may change into precancerous cells and cancerous cells may form a malignant tumor. For some men, cancerous cells may form within the prostate but grow too slowly to cause problems. In other cases, cancerous tumors may grow inside the prostate, then spread.
Prostate cancer is the most frequently diagnosed cancer and the second leading cause of death due to cancer in Canadian men [1]. During the last decade, image-guided prostate brachytherapy has become a mainstream treatment option [2,3]. Brachytherapy includes a combination of fast imaging during the insertion of hollow needles (size 18 ga) to place radioactive seeds in the diseased tissue. The radioactive seeds (about 120) destroy only a small surrounding tissue envelope. The imaging techniques include transrectal ultrasound (TRUS), endorectal coil magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopic imaging (MRSI), with TRUS being the current preferred option. Currently, the insertion of the needles during prostate brachytherapy is performed manually.
Two techniques currently exist for performing prostate brachytherapy: the “pre-planning technique” and the “real-time technique”. In both methods a post operative CT scan is required to evaluate the post procedure results, documenting seed placement and confirming that the prescribed minimum radiation dose was achieved.
The pre-planning technique requires a detailed map of the prostate prior to surgery. Using transrectal ultrasound (TRUS), physicians complete a prostate volume determination and rendering of its spatial geometry. Based on these images, a plan for seed placement is created by the medical physicist and oncologist to achieve the desired radiation dose and dose pattern (dosimetry) to the prostate. During the implant every attempt is made to duplicate the pre-planned seed pattern in the patient. Although exact duplication is never accomplished, effective results are achieved routinely by experienced brachytherapists.
The real-time planning technique requires only a preoperative sizing of the prostate. Seeds are ordered based on prostate size and radiation strength of the seeds. The detailed mapping and planning for seed implantation (dosimetry) is calculated using a nomogram calculation or computer planning software on site at the time of implantation. The real time technique has been found to be the most accurate method of placing seeds in the prostate. This method eliminates the worry about matching a patient's position to a pre plan and permits instantaneous adjustments in the operating room when the prostate gland moves”.
During prostate cancer brachytherapy about 16-30 needles are inserted in order to deliver about 60 to 120 “seeds” (small radioactive rods). The needle consists of a metal tube (18 ga or 1.25 mm diameter, 222 mm in length) with a bevelled tip and black markings at 1 cm intervals along the length. The proximal end is a plastic hub with an embossed arrow aligned with the point of the bevelled tip and a luer-lok thread. A solid rod stylette, 0.92 mm or 20 ga and length of 239 mm with black markings at 1 cm intervals, fits within the tube of the needle for the full length. The proximal end is a plastic hub. Each needle contains 1 to 6 seeds at the distal end of the tube that are usually connected by a thread. The distal end of the needle tube is plugged with wax to prevent loss of the seeds.
Brachytherapy for the treatment of prostate cancer involves the implantation of numerous radioactive seeds in a carefully pre-planned pattern in 3D within the prostate. The procedure serves to deliver a known amount of radiation dosage concentrated around the prostate, while at the same time sparing radiation-sensitive tissues such as the urethra, the bladder, and the rectum. Typically, 60 to 120 seed are placed by means of 15 to 30 needles in the inferior (feet) to superior (head) direction. These needle positions are selected from a 13×13 grid at approximately 0.5 cm evenly spaced holes in a template, which are used to achieve precise needle insertion. The numbers of these holes that intersect with the prostate cross section, and therefore are potentially usable, about 60. In current practice, the design of a suitable seed configuration which is customized to the anatomy of each patient is achieved by a specialist medical physicist or dosimetrist. The implantation is performed by an urologist or oncologist with ultrasound guidance, in consultation with a radiologist specializing in ultrasound.
The surgical team consists of two medical specialists (urologist and oncologist), an anaesthetist, a scrub nurse, an assistant nurse, a radiology technician (to operate the medical ultrasound) and a medical physicist. The order of the needle insertions and their position (coordinates on the template) is specified by the medical physicist. The scrub nurse selects the proper needle and passes to one of the specialists. This medical specialist places the needle tip into the hole of the template and pushes the needle through the skin and perineal tissue until penetrating the prostate while using the Transrectal Ultrasound (TRUS) image for guidance. Needle insertions consist of a series of pokes, sometimes accompanied by bidirectional rotation, with occasional withdrawal/retraction to reposition. The bevel of the needle tip will cause the needle to deviate from a straight trajectory which is corrected by the medical specialist. The medical specialist may use “finger direction” (the for finger presses against the needle behind the template) to modify the angle of the needle insertion. The depth and angulation of the needle tip is positioned according to a “base” defined by the distal region of the prostate as observed on the TRUS. The final position is confirmed by the other medical specialist with a ruler. The seeds are ejected from the needle by one specialist holding the stylette hub fixed while the second specialist retracts the needle barrel until the hubs contact. The needle is completely removed and placed in a waste container.
As the needle is withdrawn the seeds are deposited into the tissue. Since the needles are often deflected during insertion, 3D TRUS visualization helps to detect the deflection. Although the procedure is safe and effective it is still fraught with inadequate and inaccurate placement of the seeds. The consequences are zones of diseased tissue that are not destroyed resulting in re-growth of the cancer (requiring subsequent brachytherapy (ies)) and/or destruction of adjacent healthy cells that control the bladder sphincter muscle and/or penile erector muscles, which can result in incontinence and/or sexual dysfunction. These complications depend on the skill of the medical specialist performing the procedure.
The training of clinicians, (urologists, interventional radiologists, radiation oncologists, surgeons) would be improved by providing training simulators that mimic the morphology, mechanical properties (needle insertion) and imaging properties (ultrasound) of the tissue structures that comprise the prostate gland and adjacent tissues (skin, fascia, seminal vesicles, urethra, pelvic arch). A critical need exists is to mimic the tissues comprising the prostate by a tissue-mimicking phantom.
The use of a robot to place the seeds more accurately and quickly has been proposed. The development of this technology and the need to provide “objective evidence” that the design output meets the design parameters for regulatory submission will require stringent evaluation of this technology. There are no suitable animal models that would permit the evaluation of both the needle insertion and ultrasound guidance. A tissue-mimicking phantom would provide a simulated tissue environment for expediting the testing, refinement and validation of this technology at reduced cost.
Phantoms for medical image modalities of ultrasound, magnetic resonance imaging, computed tomography and x-ray as well as radiation therapy are reported in the literature [9-15]. All of these phantoms are intended to duplicate the image generation characteristics of tissues. The materials for these phantoms include: water, agarose gel, lipid particles, protein, glass beads, thimerosal (preservative), safflower oil, EDTA, ‘bone equivalent material’, evaporated milk, graphite particles, agar, animal hide protein, glycerol, polyurethane sponge, lexan, etc. Others [5,7] have prepared phantoms to address quality and consistency of Radiation Therapy Oncology for intensity modulated radiation therapy. There are published studies illustrating the effectiveness of hydrogels as tissue-mimicking phantoms [8].
A ‘Tissue Equivalent Ultrasound Prostate Phantom’ manufactured by CIRS [16] is commercially available. The company commented that the sole purpose of the phantom is to mimic ultrasound imaging characteristics for propagation speed and attenuation coefficient. They acknowledged that they do not know if the mechanical properties represent the mechanical forces of tissues. Since a training simulator requires a phantom with both mechanical and ultrasound imaging properties, this commercial product is not appropriate and cannot be modified to suit this application.
PVA is a polymer that can be formulated as a hydrogel with desirable properties for biomedical applications, including tissue mimicking phantoms [17,18]. In the late 1960's, PVA was cross-linked with formaldehyde to create a highly porous sponge that was marketed as Ivalon™ [12]. It was used extensively in duct replacement, articular cartilage replacement [19], as pharmaceutical release agent [12] and in reconstructive (vocal cord) surgery [20]. Although PVA can be cross-linked using glutaraldehyde, PVA has unique properties that allow it to be cross-linked by freezing and thawing (termed polyvinyl alcohol cryogel or PVA-C). The ability to modify the mechanical properties of PVA gels by physical methods (e.g. freezing/vacuum cycles) has been investigated by several authors over the past 20 years [15,21,22]. Reliable techniques for modifying the mechanical properties of PVA-C have been demonstrated [23,24]. However, some authors have indicated that PVA is not stable enough and too stiff to be suitable for application to phantoms [41].
There remains a need for a phantom for prostate cancer brachytherapy that suitably mimics the imaging and mechanical properties of a real prostate gland and its surrounding environment.